Hypoxia regulates CD44 and its variant isoforms through HIF-1α in triple negative breast cancer.
Hypoxia regulates CD44 and its variant isoforms through HIF-1α in triple negative breast cancer.
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DOI：
10.1371/journal.pone.0044078
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bhujwalla ZM
中科院分区：
文献类型：
--
作者：
Krishnamachary B;Penet MF;Nimmagadda S;Mironchik Y;Raman V;Solaiyappan M;Semenza GL;Pomper MG;Bhujwalla ZM
The CD44 transmembrane glycoproteins play multifaceted roles in tumor progression and metastasis. CD44 expression has also been associated with stem-like breast cancer cells. Hypoxia commonly occurs in tumors and is a major cause of radiation and chemo-resistance. Hypoxia is known to inhibit differentiation and facilitates invasion and metastasis. Here we have investigated the effect of hypoxia on CD44 and two of its isoforms in MDA-MB-231 and SUM-149 triple negative human breast cancer cells and MDA-MB-231 tumors using imaging and molecular characterization. The roles of hypoxia and hypoxia inducible factor (HIF) in regulating the expression of CD44 and its variant isoforms (CD44v6, CD44v7/8) were investigated in human breast cancer cells, by quantitative real-time polymerase chain reaction (qRT-PCR) to determine mRNA levels, and fluorescence associated cell sorting (FACS) to determine cell surface expression of CD44, under normoxic and hypoxic conditions. In vivo imaging studies with tumor xenografts derived from MDA-MD-231 cells engineered to express tdTomato red fluorescence protein under regulation of hypoxia response elements identified co-localization between hypoxic fluorescent regions and increased concentration of 125I-radiolabeled CD44 antibody. Our data identified HIF-1α as a regulator of CD44 that increased the number of CD44 molecules and the percentage of CD44 positive cells expressing variant exons v6 and v7/8 in breast cancer cells under hypoxic conditions. Data from these cell studies were further supported by in vivo observations that hypoxic tumor regions contained cells with a higher concentration of CD44 expression.
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DOI：
10.1186/bcr2773
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Louie E;Nik S;Chen JS;Schmidt M;Song B;Pacson C;Chen XF;Park S;Ju J;Chen EI
通讯作者：
Chen EI
影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
影响因子：
4.8
作者：
Krishnamurthy, P;Ross, DD;Schuetz, JD
通讯作者：
Schuetz, JD
影响因子：
5.2
作者：
Das, Bikul;Tsuchida, Rika;Yeger, Herman
通讯作者：
Yeger, Herman
影响因子：
6.4
作者：
Berner, HS;Suo, Z;Nesland, JM
通讯作者：
Nesland, JM